Exam 2 - Ophthalmology II (Glaucoma lecture)

Learning Objectives:

• Describe risk factors for glaucoma

• Review medication induced glaucoma

• Describe notable glaucoma trials

• Identify important diagnosing parameters

• Assess the different drug therapies available for treatment of glaucoma

What are risk factors for glaucoma?

• Increased IOP → Not necessary for diagnosis

• Optic nerve damage → Identified as C/D > 0.5

• Central corneal thickness

• Age

  • ≥60 years for general population

  • ≥40 years for African Americans

• Race → African American higher incidence

• Gender → Female > male

• Family history

  • 10x more likely to get glaucoma if family hx

  • ≥50% of glaucoma is familial

• Myopia → Not being able to see far away

• Diabetes, HTN

• Smoking, EtOH

• Hypothyroidism → Strong association

Which drugs can increase the risk of open-angle glaucoma?

Open-angle glaucoma:

• Ophthalmic corticosteroids

• Systemic/nasal/inhaled corticosteroids

• Ophthalmic anticholinergics

**Minimal risk of glaucoma if already treated with glaucoma medications and adequately controlled

**Serious risk if no treatment or inadequate treatment

Which drugs can increase the risk of angle-closure/closed-angle glaucoma?

• Topical anticholinergics and sympathomimetics (high risk)

• Systemic anticholinergics and sympathomimetics (slight risk)

• Anti-depressants – TCAs, SSRIs, imipramine, venlafaxine

• Antihistamines

What is the difference between open-angle vs angle-closure glaucoma?

Open-angle → free flow of aqueous humor

Closed-angle doesn’t allow aqueous humor to exit out

What is the etiology of glaucoma?

Anterior chamber depth is reduced, lens thickness is increased, flow of aqueous humor reduced

• Specific cause of optic neuropathy is unknown:

  • Increased IOP → Ischemia → Decreased blood flow to retina → vessel wall abnormalities → Apoptosis of retinal ganglion cells → Axonal degeneration

How is glaucoma diagnosed?

• Visual acuity test

  • How well can you see at various distances

  • Tonometer: measures pressure inside the eye

• Dilated eye exam:

  • Visualization of the retina and optic nerve

• Optic Disc → cup to disc ratio

  • C/D ≥0.5 = auto-diagnosis

• Visual Field

What is the optic disc?

It is the portion of the eye that is visible by examination as it leaves the eye

• Highly neuronal

• Cup: small depression within the disk

  • Normally does not extend beyond optic nerve rim

  • If cup-disc ratio >0.5 then indicates damage

• Alterations in disk are signs of glaucoma

Cup-to-disc (C/D) ratio of what indicates glaucoma?

C/D >0.5

How do changes in visual field change in relation to optic disc changes?

Visual field changes may lag behind optic disc changes

• Need ~25-35% of retinal ganglion cells to be damaged to detect visual field changes

• Visual field test measures peripheral vision

When a patient has glaucoma, how do we treat?

• IOP is the only factor that be managed at this time

  • Drug therapy most common first line treatment

  • Surgical intervention can be done as well

• No specific IOP but target ~30% decrease from baseline

• Lowering IOP by 1 mmHg will decrease the disease progression by roughly 10%

• IOP <18 mmHg related to reduction in visual field defects

Which agents are used for the treatment of glaucoma?

• Beta-blockers (1st line)

• Prostaglandin analogs (1st line)

• Alpha-2 adrenergic agonists

• Carbonic Anhydrase Inhibitors (CAIs)

• Parasympathomimetic agents

• Non-specific adrenergic agonists

• Rho Kinase Inhibitor

What is the MOA of beta-blockers? How much do they lower IOP?

• Lower IOP by 20-30%

  • All lower IOP to a similar degree

• Mechanism of Action: Reduce the aqueous humor production of the ciliary body

• If no contraindications, commonly used as first line

Which optic beta-blockers are used? How frequently can we use them?

• Timolol → non-selective

• Betaxolol → B1-selective

• Carteolol → non-selective

• Levobunolol → non-selective

• Metipranolol → Non-selective

All are dosed 1 drop BID

Long-term use of beta-blockers can result in what?

Tachyphylaxis → can stop working overtime

• If tachyphylaxis occurs, switch to different beta-blocker or different class

What are ADRs associated with beta-blocker use?

• Topical ADRs:

  • Dry eyes, corneal anesthesia, blepharitis

  • Blurred vision, stinging

• Systemic ADRs:

  • Decreased heart rate, decreased blood pressure, negative inotropic effects

  • Bronchospasm, block symptoms of hypoglycemia

• Reduce sx by use of punctal occlusion, eyelid closure

Beta-blockers should be used with CAUTION in which patients?

• Pulmonary disorders

• Cardiovascular diseases (CHF, sinus bradycardia, 2nd/3rd degree heart block)

• Diabetes

• Use of oral beta-blockers

What is the MOA of prostaglandin & prostamide analogs?

• Mechanism of action: Decrease IOP by increasing the uveoscleral outflow of the aqueous humor and to a lesser extent trabecular outflow

Productive-specific:

• Latanoprostene bunod: releases nitric oxide which can relax the trabecular meshwork increasing drainage of aqueous humor

• Omidenepag isopropyl: hydrolyzes to active omidenepag working in both uveoscleral and trabecular outflow

  • Prodrug

Which products are prostaglandin analogs?

• Latanoprost

• Latanoprostene bunod

• Travaprost

• Tafluprost

Which product is a prostamide analog?

Bimatoprost

Which product is our selective E2 analog?

Omidenepag isopropyl (prodrug)

Which prostaglandin analog comes as both a solution AND emulsion?

Latanoprost (Xalatan, Iyuzeh) = solution

Latanoprost (Xelpros) = emulsion

How often are prostaglandin/Prostamide Analogs used?

1 gtt qHS (1 drop at bedtime)

• Used once daily

GOOD FOR ADHERENCE

How much do Prostaglandin & Prostamide Analogs lower IOP?

Lowers IOP ~25-35% → our strongest agent

How should Prostaglandin & Prostamide Analogs be stored?

Latanoprost, latanoprostene bunod, tafluprost, omidenepag must be stored in refrigerator until opened

• Then stable for 6 weeks at room temperature

Which preservatives do our prostaglandin & prostamide analogs contain?

• Latanoprost, latanoprostene bunod, and bimatoprost contain → benzalkonium chloride

• Travoprost contains → Sofzia

• Latanoprost (Xelpros®) contains potassium sorbate

• Tafluprost and Iyuzeh brand® → preservative free!

Which Prostaglandin & Prostamide Analogs come as implants?

• Bimatoprost (Durysta®) 10cmg: to be used only once in each eye

  • Biodegradable dissolving in 6 months

  • Only once per eye per lifetime

• Travoprost (iDose TR®) 75mcg

  • Provide up to 3 years of therapy

  • Is MRI conditional → patients should notify they have this implant to any pending MRI

What ADRs are associated with prostaglandin & prostamide analog use? ***KNOW

Generally well tolerated, local ocular tolerance is good

• 1) Altered iris pigmentation

  • More prone in mixed color irises (blue-brown, greenbrown, blue-gray-brown, yellow-brown)

  • Irreversible

• 2) Hypertrichosis (longer/thicker eye lashes)

  • Common and reversible once agent is d/c’ed

• 3) Hyperpigmentation around lids

  • Reversible once agent is d/c’ed

What is Latisse?

• Bimatoprost 0.03%

• Used for hypotrichosis

• Applied nightly directly to the skin of the upper eyelid margin at the base of the eyelashes using the accompanying applicators

• Can also cause hyperpigmentation of the eyelids and iris color changes

What is the role of alpha-2 adrenergic agonists?

Not 1st line, moreso 3rd-line after beta-blocker & prostaglandins

Which alpha-2 adrenergic agonists do we use?

• Brimonidine (Alphagan P)

• Apraclonidine (not used anymore)

• Mechanism of action:

  • Reduce aqueous humor production

  • Brimonidine also increases uveoscleral outflow

How frequently can alpha-2 adrenergic agonists be used?

1 drop BID-TID (2-3x/day)

How much do alpha-2 agonists reduce IOP?

Reduce IOP by 18-27% at peak (2-5 hours) and 10% (8-10 hours)

Briomnidine (Alphagan P) contains prurite preservative, how is this beneficial?

• More neutral pH → if more neutral, more absorption

• Less ocular allergy

• Increased bioavailability

Which ADRs are associated with alpha-2 adrenergic agonists?

• Allergic type reaction: lid edema, eye discomfort, foreign-body sensation, itching, hyperemia → D/C if these occur

• Systemic

  • Dizziness, fatigue, somnolence, dry mouth, potential to lower blood pressure/pulse

  • Use with CAUTION if have cardiovascular disease, cerebrovascular disease

    • Or if taking antihypertensives, MAO-Is, TCAs

What is Lumify? What is it use for?

• Brimonidine 0.025% (OTC product)

• Redness remover

  • Works in 1 minute and lasts 8 hours

  • Selectively constricts the venule and maintains oxygenation to surrounding tissue

What is good about lumify?

Is selectively constricts the venule only

• Other products constrict the arterioles, leading to REBOUND CONGESTION

What is role of therapy of carbonic anhydrase inhibitors? (CAIs)

“3rd line agents”, available as both topical and oral formulation

What is the MOA of CAIs?

• Mechanism of action: Blocks active secretion of the sodium and bicarbonate ions from the ciliary body to the aqueous humor

• Reduces IOP by 15-26% (topical use)

  • Systemic lowers IOP by 25-40% and reduces aqueous humor inflow by 40-60%

    • Systemic CAIs are more effective - but have lots of more side effects

What are the CAI agents used?

• Brinzolamide (Azopt) → Suspension

  • 1 gtt BID-TID (2-3x/day)

• Dorzolamide (Trusopt) → Solution

  • 1 gtt BID-TID (2-3x/day)

• Acetazolamide → Tablet, capsule, or injection

  • 1 tab BID-QID (2-4x/day)

• Metazolamide → Tablet

  • 1 tab BID-TID (2-3x/day)

What are side effects associated with topical CAIs?

Topical formulations tolerated well

• Transient burning/stinging/blurring/tearing

• Blurry vision: Brinzolamide > dorzolamide

• Stinging: Dorzolamide > brinzolamide

A patient complains of blurry vision using CAIs. Between Brinzolamide and Dorzolamide, which one is better for blurry vision?

Brinzolamide has less blurry vision side effects

A patient complains of stinging using CAIs. Between Brinzolamide and Dorzolamide, which one is better for stinging?

Dorzolamide has less stinging

What is the place in therapy of systemic CAIs?

• Indicated for patients failing to respond to or tolerating maximum topical therapy

  • “Last line agents”

• Should NOT be used in combination with topical CAIs

Which systemic side effects are seen with CAIs?

• Only 30-60% able to tolerate oral agents

• Malaise, fatigue, depression, confusion

• N/V/D, anorexia, weight loss, metallic taste***

• Systemic acidosis, electrolyte imbalance

• Renal calculi (stones), increased uric acid

• Blood dyscrasias

Which patients should we use CAIs with caution?

• Patients with SULFA allergies

• Also in pulmonary disorders, hepatic/renal disease, history of renal calculi for oral formulation

  • Contraindicated in ESRD pr severe renal impairment

What is the role of parasympathomimetic agents?

“Last line agents”

• Not used as often due to adverse events and frequent dosing regimens

• Mechanism of action:

  • Increase the aqueous humor trabecular outflow

  • May reduce uveoscleral outflow

Which parasympathomimetic agents do we use?

• Carbachol → solution

  • 1 drop BID-TID

• Pilocarpine → solution and gel

  • Solution: 1 drop BID-TID

  • Gel: 1 drop qHS

Pilocarpine is preferred over carbachol

Which ADRs are seen with Parasympathomimetic Agents?

• Miosis (constriction of pupil) decreased night-time vision

• Frontal headache, brow ache, periorbital pain

• Eyelid twitching, conjunctival irritation or injections early in therapy

• All of the above are more frequent, constant, and severe with carbachol → therefore, pilocarpine preferred

What is our rho kinase inhibitor?

• Netarsudil (Rhopressa®) 0.02% solution

  • 1 gtt daily in evening

• Reduces IOP up to 5 mmHg

• Mechanism of Action: inhibits rho kinase enzymes thereby increasing drainage of intraocular fluid through trabecular meshwork

• Adverse Events: hyperemia, corneal deposits, stinging, mild conjunctival hemorrhage

What should we monitor when giving treatment for glaucoma?

• Start with one medication

• Follow-up in 2-4 weeks

• Once reach target IOP then q3-6 months

• Visual field and disk changes annually

• No single agent is labeled as drug of choice first line

• If partial response → ADD-ON therapy with a second agent

• If no response → SWITCH to an alternative agent after 1 day of concurrent therapy

• Maximum medical therapy would be ~3 meds per day

  • Ex: prostaglandin + combination product

• No specific IOP but would target:

  • ~20% mild glaucoma, 30-40% moderate, 50% severe

What is classified as ocular hypertension?

Elevated IOP (>22 mmHg) but no disk changes or visual field loss

• Based on risk factors:

  • If IOP >26 mmHg, cup-disc ratio >0.3, central corneal thickness <555 micrometers are at risk of developing glaucoma → TREAT

  • Family history, race, severe myopia, only one eye increased consideration

  • If no risk factors, typically not treated